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Biomedical subjects

Y Yin

Publications and source records attributed to Y Yin.

At least 55 records · Page 3Linked to original sources

Lens injury stimulates axon regeneration in the mature rat optic nerve.

In mature mammals, retinal ganglion cells (RGCs) are unable to regenerate their axons after optic nerve injury, and they soon undergo apoptotic cell death. However, a small puncture wound to the lens enhances RGC survival and enables these cells to regenerate their axons into the normally inhibitory environment of the optic nerve. Even when the optic nerve is intact, lens injury stimulates macrophage infiltration into the eye, Müller cell activation, and increased GAP-43 expression in ganglion cells across the entire retina. In contrast, axotomy, either alone or combined with intraocular injections that do not infringe on the lens, causes only a minimal change in GAP-43 expression in RGCs and a minimal activation of the other cell types. Combining nerve injury with lens puncture leads to an eightfold increase in RGC survival and a 100-fold increase in the number of axons regenerating beyond the crush site. Macrophage activation appears to play a key role, because intraocular injections of Zymosan, a yeast cell wall preparation, stimulated monocytes in the absence of lens injury and induced RGCs to regenerate their axons into the distal optic nerve.

Animals↗

Analysis of p53-regulated gene expression patterns using oligonucleotide arrays.

Oligonucleotide microarrays were employed to quantitate mRNA levels from a large number of genes regulated by the p53 transcription factor. Responses to DNA damage and to zinc-inducible p53 were compared for their transcription patterns in cell culture. A cluster analysis of these data demonstrates that genes induced by gamma radiation, UV radiation, and the zinc-induced p53 form distinct sets and subsets with a few genes in common to all these treatments. Cell type- or cell line-specific p53 responses were detected. When p53 proteins were induced with zinc, the kinetics of induction or repression of mRNAs from p53-responsive genes fell into eight distinct classes, five different kinetics of induction, and three different kinetics of repression. In addition, low levels of p53 in a cell induced or repressed only a subset of genes observed at higher p53 levels. The results of this study demonstrate that the nature of the p53 response in diverse mRNA species depends on the levels of p53 protein in a cell, the type of inducing agent or event, and the cell type employed. Of 6000 genes examined for p53 regulatory responses, 107 induced and 54 repressed genes fell into categories of apoptosis and growth arrest, cytoskeletal functions, growth factors and their inhibitors, extracellular matrix, and adhesion genes.

Chlorides↗

Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells.

Bloom syndrome (BS) is characterized by genomic instability and cancer susceptibility caused by defects in BLM, a DNA helicase of the RecQ-family (J. German and N. A. Ellis, The Genetic Basis of Human Cancer, pp. 301-316, 1998). RecQ helicases and topoisomerase III proteins interact physically and functionally in yeast (S. Gangloff et al., Mol. Cell. Biol., 14: 8391-8398, 1994) and in Escherichia coli can function together to enable passage of double-stranded DNA (F. G. Harmon et al., Mol. Cell, 3: 611-620, 1999). We demonstrate in somatic and meiotic human cells an association between BLM and topoisomerase IIIalpha. These proteins colocalize in promyelocytic leukemia protein nuclear bodies, and this localization is disrupted in BS cells. Thus, mechanisms by which RecQ helicases and topoisomerase III proteins cooperate to maintain genomic stability in model organisms likely apply to humans.

Adenosine Triphosphatases↗

Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.

TLS (also known as FUS) is an RNA-binding protein that contributes the N-terminal half of fusion oncoproteins implicated in the development of human liposarcomas and leukemias. Here we report that male mice homozygous for an induced mutation in TLS are sterile with a marked increase in the number of unpaired and mispaired chromosomal axes in pre-meiotic spermatocytes. Nuclear extracts from TLS(-/-) testes lack an activity capable of promoting pairing between homologous DNA sequences in vitro, and TLS(-/-) mice and embryonic fibroblasts exhibit increased sensitivity to ionizing irradiation. These results are consistent with a role for TLS in homologous DNA pairing and recombination.

Animals↗

Identification and expression of mouse netrin-4.

Netrins are secreted proteins that serve as potent axon guidance molecules in vertebrates and invertebrates. We report the identification of a novel mammalian member of this family. Netrin-4 is similar in predicted size and secondary structure to the other three netrins; all contain, in order, an amino-terminal signal sequence, a laminin-type globular domain of the 'VI' type, three laminin-type epidermal growth factor (EGF) repeats, and a carboxyl-terminal 'netrin module'. In terms of primary sequence, however, netrin-4 is a distant relative of netrins-1-3, and its globular domain is more closely related to those of laminins than to those of other netrins. Netrin-4 is broadly expressed in both neural and non-neural tissues of embryonic and adult mice. In embryonic spinal cord, it is selectively expressed by cells at the lateral margins of the floor plate. In postnatal brain, it is selectively expressed in subsets of neurons, including cerebellar granule and hippocampal pyramidal cells.

Age Factors↗

Stability of family interaction from ages 6 to 18.

Research has demonstrated the stability of juvenile offending during childhood and adolescence but generally has not focused on the continuity of family interactions associated with juvenile offending. The present report focused on the stability of several family interaction events and attributes (i.e., physical punishment, communication, supervision, positive parenting, and parent-child relationship) for a large sample of male adolescents and their primary caretakers, drawn from a multiyear longitudinal study that represented middle childhood through late adolescence (ages 6-18). We also assessed the impact of ethnicity, family composition, teenage motherhood, and youth delinquency on these interactions. Test-retest correlations and growth-curve analyses were used to assess relative and absolute stability of the interactions, respectively. As predicted, relative stability of family interaction was high. There was an absolute change in scores of physical punishment (decreased) compared to poor supervision and low positive parenting (both increased), whereas poor communication and bad relationship with the caretaker did not measurably change with age. Single-parent families and families with teenage mothers experienced significantly worse interactions over time than did families consisting of two biological parents present in the household. These findings are discussed in relation to the development of juvenile offending.

Adolescent↗

The effects of lamotrigine on the pharmacokinetics of lithium.

AIMS: The treatment of bipolar disorder often includes use of multiple drug therapies. Lithium is one of the most commonly used treatments, but has a narrow therapeutic window. Lamotrigine, an established antiepileptic drug, is emerging as a potentially important new therapy in the treatment of bipolar disorder. The objective of this two-treatment crossover study was to determine whether lamotrigine affects lithium pharmacokinetics. METHODS: Twenty healthy adult men completed the study. Subjects took 2 g lithium gluconate anhydrous every 12 h in the morning and evening for 5 days and in the morning of day 6, with or without 100 mg lamotrigine once daily in the morning for 6 days. Blood and urine samples were collected on day 6 of both treatments to characterize the pharmacokinetics of lithium using noncompartmental methods. RESULTS: The geometric least-square mean ratio for renal clearance of lithium between the combination treatment and lithium alone treatment was 0.93 (95% confidence interval 0.85-1.02). Both treatments were well tolerated. CONCLUSIONS: Lamotrigine does not cause significant change in the pharmacokinetics of lithium.

Adult↗

Constitutive levels of cAMP-dependent protein kinase activity determine sensitivity of human multidrug-resistant leukaemic cell lines to growth inhibition and apoptosis by forskolin and tumour necrosis factor alpha.

The cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) signal pathway regulates cell proliferation, differentiation and cell death. It may also regulate the multidrug resistance (MDR) phenotype in leukaemic cells. These data showed that MDR1+ K/Dau600 cells exhibited a higher basal level of PKA activity than MDR- parental cells. The significance of this on tumour necrosis factor alpha (TNFalpha)-induced apoptosis and cytostasis was investigated further. In comparison with MDR1- parental cells, K/Dau600 cells had a higher expression of PKA regulatory subunit RIalpha and nuclear catalytic subunit PKAcalpha. They were also more susceptible to inhibition of proliferation and induction of apoptosis by TNFalpha and/or forskolin, but this could be attenuated by H89. An increase in cAMP was associated with the apoptosis in the K/Dau600 cell line. Forskolin inactivated NF-kappaB in K/Dau600 cells but not in K562 cl. 6 cells, whereas TNF activated NF-kappaB in K562 cl.6 cells but not in K/Dau600 cells. 8-Cl-cAMP exhibited similar inhibitory effects on the proliferation of all of the cell lines used via its metabolite 8-Cl-adenosine, which indicates that these effects were independent of residual PKA or cAMP. Therefore, the differential sensitivity to apoptosis and/or growth inhibition could be mediated via cAMP, partly through PKA via NF-kappaB and partly by PKA-independent pathways.

8-Bromo Cyclic Adenosine Monophosphate↗

2.9 A crystal structure of ligand-free tryptophanyl-tRNA synthetase: domain movements fragment the adenine nucleotide binding site.

The crystal structure of ligand-free tryptophanyl-tRNA synthetase (TrpRS) was solved at 2.9 A using a combination of molecular replacement and maximum-entropy map/phase improvement. The dimeric structure (R = 23.7, Rfree = 26.2) is asymmetric, unlike that of the TrpRS tryptophanyl-5'AMP complex (TAM; Doublié S, Bricogne G, Gilmore CJ, Carter CW Jr, 1995, Structure 3:17-31). In agreement with small-angle solution X-ray scattering experiments, unliganded TrpRS has a conformation in which both monomers open, leaving only the tryptophan-binding regions of their active sites intact. The amino terminal alphaA-helix, TIGN, and KMSKS signature sequences, and the distal helical domain rotate as a single rigid body away from the dinucleotide-binding fold domain, opening the AMP binding site, seen in the TAM complex, into two halves. Comparison of side-chain packing in ligand-free TrpRS and the TAM complex, using identification of nonpolar nuclei (Ilyin VA, 1994, Protein Eng 7:1189-1195), shows that significant repacking occurs between three relatively stable core regions, one of which acts as a bearing between the other two. These domain rearrangements provide a new structural paradigm that is consistent in detail with the "induced-fit" mechanism proposed for TyrRS by Fersht et al. (Fersht AR, Knill-Jones JW, Beduelle H, Winter G, 1988, Biochemistry 27:1581-1587). Coupling of ATP binding determinants associated with the two catalytic signature sequences to the helical domain containing the presumptive anticodon-binding site provides a mechanism to coordinate active-site chemistry with relocation of the major tRNA binding determinants.

Adenine Nucleotides↗

Tumor suppressor p53 is required to modulate BRCA1 expression.

Individuals carrying mutations in BRCA1 or p53 genes are predisposed to a variety of cancers, and both tumor suppressor genes have been implicated in DNA damage response pathways. We have analyzed a possible functional link between p53 and BRCA1 genes. Here we show that BRCA1 expression levels are down-regulated in response to p53 induction in cells that undergo either growth arrest, senescence, or apoptosis. Physiological stimuli, such as exposure to DNA-damaging agents, also result in negative regulation of BRCA1 levels in a p53-dependent manner prior to causing cell cycle arrest. Nuclear run-on experiments and luciferase reporter assays demonstrate that the changes in BRCA1 expression are mainly due to transcriptional repression induced by p53. In conclusion, the data show that BRCA1 expression levels are controlled by the presence and activity of wild-type p53 and suggest the existence of an intracellular p53/BRCA1 pathway in the response of cells to stress conditions.

Animals↗

The effect of nerve-root injections on the need for operative treatment of lumbar radicular pain. A prospective, randomized, controlled, double-blind study.

BACKGROUND: The purpose of the present study was to determine the effectiveness of selective nerve-root injections in obviating the need for an operation in patients with lumbar radicular pain who were otherwise considered to be operative candidates. Although selective nerve-root injections are used widely, we are not aware of any prospective, randomized, controlled, double-blind studies demonstrating their efficacy. METHODS: Fifty-five patients who were referred to four spine surgeons because of lumbar radicular pain and who had radiographic confirmation of nerve-root compression were prospectively randomized into the study. All of the patients had to have requested operative intervention and had to be considered operative candidates by the treating surgeon. They then were randomized and referred to a radiologist who performed a selective nerve-root injection with either bupivacaine alone or bupivacaine with betamethasone. The treating physicians and the patients were blinded to the medication. The patients were allowed to choose to receive as many as four injections. The treatment was considered to have failed if the patient proceeded to have the operation, which he or she could opt to do at any point in the study. RESULTS: Twenty-nine of the fifty-five patients, all of whom had initially requested operative treatment, decided not to have the operation during the follow-up period (range, thirteen to twenty-eight months) after the nerve-root injections. Of the twenty-seven patients who had received bupivacaine alone, nine elected not to have the operation. Of the twenty-eight patients who had received bupivacaine and betamethasone, twenty decided not to have the operation. The difference in the operative rates between the two groups was highly significant (p < 0.004). CONCLUSIONS: Our data demonstrate that selective nerve-root injections of corticosteroids are significantly more effective than those of bupivacaine alone in obviating the need for a decompression for up to thirteen to twenty-eight months following the injections in operative candidates. This finding suggests that patients who have lumbar radicular pain at one or two levels should be considered for treatment with selective nerve-root injections of corticosteroids prior to being considered for operative intervention.

Anesthetics, Local↗

99mTc-MIBI and 99mTc-MDP scintimammography for detecting breast carcinoma.

OBJECTIVE: To assess the value of scintimammography with both 99mTc-MIBI and 99mTc-MDP in detecting breast cancer. METHODS: A total of 35 women with clinical findings of suspicious breast lesions were studied with both 99mTc-MIBI and 99mTc-MDP scintimammography. All patients underwent surgery within one week and the final diagnostic results (histopathological) were obtained. RESULTS: Eighteen of 35 abnormalities of breast were pathologically confirmed as breast cancer and 17 as benigN lesions. In this group of patients studied, the sensitivity, specificity and accuracy of 99mTc-MIBI scintimammography were 77.8%, 88.2% and 82.9%, respectively and those of 99mTc-MDP scintimammography were 72.2%, 88.2% and 80.0%, respectively. There was no significant difference between 99mTc-MIBI and 99mTc-MDP scintimammography. CONCLUSION: This study showed the high diagnostic accuracy of both 99mTc-MIBI and 99mTc-MDP scintimammography in detecting breast cancer. Both can be used as non-invasively assess breast cancer invasiveness before surgery.

Adult↗

[Management of the neck for patients with thyroid papillary carcinoma].

OBJECTIVE: To search an optimal management of the neck for patients with thyroid papillary carcinoma. METHODS: Clinical data of 424 cases with thyroid papillary carcinoma treated in our hospital from Jan, 1965 to Jan, 1987 were analyzed retrospectively. Patients with positive cervical lymph nodes (N+) were treated with radical excision of the primary tumor and neck dissection. For patients without cervical lymph node involvement (N0), neck dissection was spared. On follow-up, whenever cervical lymphatic node metastasis occurred, neck dissection was performed. All patients were followed up for more than 10 years. RESULTS: The 5- and 10-year survival rate of the 258 N+ patients was 84.3% and 80.4% respectively, and that of the 166 N0 patients was 94.1% and 91.3% respectively. Twenty-three N0 cases later developed cervical lymph node metastasis. Their 5- and 10-year survival rate was 91.4% and 82.2% respectively after neck dissection. CONCLUSION: Since only 13.9% of N0 thyroid papillary carcinoma patients who did not receive neck dissection develop cervical lymph node metastases later, and their survival rate was just as good where neck dissection is postponed until metastases occur, prophylactic neck dissection seems unnecessary.

Adolescent↗

[The influence of different root length on stress distribution in the bone around abutment root of telescopic overdenture].

OBJECTIVE: To investigate the influence of bone height around the roots on stress distribution in a mandible with two canines remained and covered with an telescopic overdenture. METHODS: Three-dimensional finite element method. RESULTS: As the height of the bone around the roots decreased, the stress increased. But the maximum stress in the bone in this study is lower than that in the bone around the canine under normal condition. CONCLUSION: In the mandible, when the alveolar bone resorption reaches the apical 1/3 of canine (root length 4, 5 mm), if part of the tooth crown was removed, to make an acceptable crown/root ratio, so the canine can be used as the abutment of an overdenture.

Compressive Strength↗

[Immunohistochemical findings on liver tissue in patients with hepatitis C].

OBJECTIVE: To investigate the distributions and infer relations of HCV antigens in the liver tissues. METHODS: Immunohistochemical techniques as polyclonal antibody to HCV, monoclonal antibody to HCV - NS3 and monoclonal antibody to HCV - NS5 were used to detect HCV antigens in 107 patients with hepatitis C. RESULTS: HCV antigens in liver tissues were identified on these three kinds of antibodies. The positive rates were 38.3%, 28.0% and 52.3% respectively. The positive granules were located in the cytoplasma of liver cells. The distributions of positive cells were scattered, diffusive and clustered. No obvious anatomic association was observed between the expression of HCV - NS3 and inflammatory reaction. HCV - NS5 positive cells were more commonly seen around or in the flammatory focci. CONCLUSION: The expressions of various components of HCV were demonstrated in different concentrations. The expressions of HCV - NS5 might be related to the pathogenesis of hepatitis C.

Adult↗

[The hereditary liability of otosclerosis and the strategies for treatment and prevention].

OBJECTIVE: Otosclerosis is a disease of hereditary liability. It might be related to an autosomal dominant inheritance. The genetic penetrance is determined by multifactorial influences. This paper was designed to study the reasonable strategies for prevention and treatment of this disease. METHODS: A retrospective review derived from data of the management and follow-up of 14 cases in 6 families. According to the special pathological features of active phase of the otospongiosis, the suitable strategies for prevention and treatment of this disease were suggested. RESULTS: Diagnosis of 14 cases were confirmed by audiological, operative and/or pathological examinations. Eleven of fourteen cases underwent stapedectomy, in which 10 cases had the surgery on the ear with severer hearing loss, and one case on both sides. In all of the surgical cases, hearing levels improved significantly. Three cases have not yet received the stapedectomy, in which two cases scheduled for the surgery are currently treated by chondroitin sulfate and one case refused the surgical treatment due to financial shortage. CONCLUSION: Examination of the ear function at regular intervals (6-12 months) is recommended for the adults among the family members with high-incidence of otosclerosis. Audiological and radiological examination play an important role in early diagnosis and treatment. Attention should be paid to the medicine for management and prevention of this disease. Stapedectomy is an optimal choice for clinical otosclerosis not only due to its capacity to improve the hearing level but also to prevent the advance of hearing loss. Hearing aid is the suitable choice if stapedectomy is contraindicated.

Audiometry↗

[The time-delay fluorescence phenomenon of SrFCl0.5Br0.5:Sm2+].

In this paper the Sm2+ fluorescence spectra SrFCl0.5Br0.5:Sm2+ is reported. Based on some stronger fluorescence peaks of time-distinguished spectra, the life of the fluorescence is achieved. Compared the fluorescence spectra stimulated by the continuous light with the fluorescence spectra stimulated by pulse, the phenomenon of delay fluorescence is discovered and it's reason comes from particle distribution of different energy levels.

English Abstract↗